SURVEILLANCE STRATEGIES FOR COLON CANCER
Screening of patients at increased risk of colon cancer is likely to prevent early death, but large-scale studies are of course difficult to conduct. In Finland, one study has found that Lynch syndrome family members who undergo colonoscopy have a much lower CRC incidence rate, probably due to removal of adenomas. The overall death rates were 10 versus 26 subjects in the study and control groups (P = 0.003) and 4 versus 12 in mutation- positive subjects (P = 0.05) (Jarvinen et al. 2000). In addition, the benefits of a genetic register for ascertaining and coordinating the screening of individuals at risk for familial adenomatous polyposis are now well recognized (Kinzler and Vogelstein 1996; King et al. 2000; Vasen et al. 2008).
In a significant proportion (approximately 30 %) of families that meet the Amsterdam criteria, the results of the MSI and IHC analysis of the colorectal Tumours(s) are negative. Clustering of CRC by chance or genetic factors other than Lynch syndrome may be responsible for the disease in these families, which are characterized by a more advanced age of onset of CRC than in families with Lynch syndrome, and the absence of endometrial cancer and multiple Tumours. The risk of developing CRC in such families is increased only by a factor of 2.3, so a less-intensive colonoscopic surveillance program (e.g., colonoscopy every 5 years, starting 5–10 years before the first diagnosis of CRC or at 45 years) might be appropriate (Vasen et al. 2007, 2009; Järvinen et al. 2008). The close relatives of those found to have no evidence of Lynch syndrome, but where there is a family history of later-onset CRC, have a higher CRC risk where the CRC is microsatellite unstable (Aaltonen et al. 2007).
Predictive testing for Lynch syndrome is now available for the presymptomatic diagnosis of this condition in families in which the pathogenic mutation has been defined, so that it is becoming possible to target high-risk asymptomatic individuals for screening, as for familial adenomatous polyposis. Guidelines for screening individuals at risk for Lynch syndrome are regular colonoscopy (every 1–2 years) from the age of 25 years, and those with a family history that includes cancers at other sites, including endometrium, should be offered screening for other cancers as appropriate (Vasen et al. 2010a). In addition to detecting presymptomatic colonic carcinomas, such screening allows the endoscopic detection and removal of adenomas. It is presumed (but not proven) that most cancers in patients with Lynch syndrome arise from adenomas and that excision of the latter will prevent the development of colon cancer.
Colonoscopy is the investigation of choice because of the preponderance of right-sided Tumours in this condition (Vasen et al. 2013).
In familial CRC families without evidence for Lynch syndrome, surveillance for CRC should take into account the financial costs of screening and the possibility of adverse effects of screening by colonoscopy in particular and balance this with the individual’s estimated risk of CRC (Johnson et al. 2008). Cairns et al. (2010) have published family history criteria for individuals at high–moderate and low–moderate risk of developing colorectal cancer based on the polygenic inheritance model and have advocated screening protocols based on these groupings. Briefly, individuals assessed as being at high–moderate risk may have three affected relatives at any age, in a first-degree kinship, or two affected relatives diagnosed below 60 years of age. Individuals at low–moderate risk would be those with one affected relative diagnosed before 50 years of age or two diagnosed over the age of 60 years of age. They advocated that the high– moderate risk group should have 5 yearly colonoscopies from 50 years of age and the low–moderate risk group one colonoscopy at 55 years of age, and no further investigations unless polyps were detected at the screening colonoscopy (Table5.6). These guidelines for screening in those at moderately increased risk of CRC as assessed by family history have been updated in the UK, commissioned by the British Society of Gastroenterology and the Association of Coloproctology for Great Britain and Ireland, based on literature review and expert opinion (Cairns et al. 2010). They take into account the fact that the risks of colonoscopy are small but significant (Williams and Fairclough 1991); in a population-based study, serious complications were recorded in 2 per 1,000 colonoscopies (Gatto et al. 2003). The 14-day death rate is around 5–10 % of the perforation rate, or 0.83 per 10,000 procedures (CI 0.025–3.69), and 3.9 per 10,000 (CI 1.1–8.8) after polypectomy (Anderson et al. 2000; Gatto et al. 2003). The perforation rate after polypectomy is quoted as 22 (CI 13.8–33.3) per 10,000, with post- polypectomy bleeding in a further 89 (CI 71.5–109.5) per 10,000 (Cairns et al. 2010; Zha et al. 2004; Imperiale et al. 2008).
Table 1 Screening guidelines for colon cancer in individuals with a moderate family history of CRC: a guide for the gastroenterologist and colorectal surgeon
|CRC in 3 FDR in 1st-degree kinship, none diagnosed <50 years of age||Colonoscopy 5 yearly||From 50 to 75 years of age|
|CRC in 2 FDR in 1st-degree kinship, mean age <60 years of age||Colonoscopy 5 yearly||From 50 to 75 years of age|
|CRC in 2 FDR diagnosed >60 years of age||Single colonoscopy||Once at 55 years of age; no more if normal|
|CRC in 1 FDR diagnosed <50 years of age||Single colonoscopy||Once at 55 years of age; no more if normal|
|Other FH CRC unless diagnostic of Lynch||No screening|
|Amsterdam criteria positive||Refer to genetics center|
|Incident CRC cases diag. <50 years of age or MSI+, not Amsterdam criteria positive||Arrange MSI/IHC, consider referral to genetics center|
|FAP/MUTYH polyposis||Refer to genetics center|
Adapted from Cairns et al. (2010)
FDR first-degree relative, SDR second-degree relative
Some newer forms of colonoscopic surveillance in Lynch syndrome have been advocated but are not yet in widespread use (Haanstra et al. 2013).